Immune-based Response Research Articles

A Review on the Recent Advancements of Zinc Oxide Based Compounds in Different Applications

Nanomaterials technology and development have successfully served progress various scientific areas. Because of its biocompatibility, special physicochemical characteristics and cost-effective mass production, zinc oxide (ZnO)-based nanocomposites has been the most viable techniques for biological applications. Latest developments in nano-engineering, moreover, technology enables the generation of specific three-dimensional structures and surface properties of ZnO nanocomposites which are efficiently developed on behalf of in vivo tests. Herein, our study showed current developments on the use of various ZnO NCs, by a specific emphasis of use. Production like immunotherapeutic vaccines adjuvants and tumor, and also their interfacial properties that interfere with both the immune system and the in vivo possible toxic impact. Eventually, as therapeutic and preventive vaccines towards pathogens, we summarise promising evidence-of-concept applications towards cancer. Moreover, the analysis of these composites is of highly significance due to their enhanced multifunctional properties, such as their mechanical, filter and antibacterial activities, the food processing materials sector. The knowledge of a nano-based biological frameworks among ZnO-based NCs and their immune-based response, along with the biologically effective strategy of nanomaterials by means of nano-architectural expertise, may open novel opportunities for the expansion of the therapeutic use of ZnO nanocomposites as an innovative platform for vaccines.

Vertically Transmitted Gut Bacteria and Nutrition Influence the Immunity and Fitness of Bactrocera dorsalis Larvae.

Symbiotic bacterial communities that colonize the digestive tract of tephritid fruit flies interact with nutrient intake to improve the flies’ fitness and immunity. Some bacterial species consistently inhabit the tephritid guts and are transmitted to the next generation vertically. These species contribute significantly to some aspects of their host’s physiology. In the current study, we examined the role of four vertically transmitted bacteria (Citrobacter, Enterobacter, Klebsiella, and Providencia) on the fitness parameters and immunity of Bactrocera dorsalis larvae that were fed a nutritionally manipulated diet. For this purpose, eggs were collected from axenic, gnotobiotic, and symbiotic adult flies, and larvae were reared on four types of diets in which carbohydrate and/or protein contents were reduced and then compared with larvae raised on a control diet. The diet and bacterial interactions significantly affected the fitness and immunity of B. dorsalis. Larvae of axenic flies grew slower and displayed weaker immune-based responses (PO activity, antibacterial activity, survival) than larvae of gnotobiotic and symbiotic flies. Overall, larvae reared on the low-protein diet grew slower than those reared on the control or low-carbohydrate diets. Survival, PO activity, and antibacterial activity were significantly lower in the hemolymph of larvae reared on low-protein diets. Our results also revealed that the levels of hemolymph protein, glucose, trehalose, and triglyceride in larvae from axenic flies were significantly lower than those in larvae of the symbiotic group after they fed on most of the tested diets. These results strongly infer that diet and vertically transmitted bacteria are both essential contributors to the fitness and immunity of B. dorsalis.

An immune-based response particle swarm optimizer for knapsack problems in dynamic environments

This paper proposes a novel binary particle swarm optimization algorithm (called IRBPSO) to address high-dimensional knapsack problems in dynamic environments (DKPs). The IRBPSO integrates an immune-based response strategy into the basic binary particle swarm optimization algorithm for improving the quantity of evolutional particles in high-dimensional decision space. In order to enhance the convergence speed of the IRBPSO in the current environment, the particles with high fitness values are cloned and mutated. In addition, an external archive is designed to store the elite from the current generation. To maintain the diversity of elites in the external archive, the elite of current generation will replace the worst one in the external archive if and only if it differs from any of the existing particles in the external archive based on the Hamming distance measurement when the archive is due to update. In this way, the external archive can store diversiform elites for previous environments as much as possible, and so as to the stored elites are utilized to transfer historical information to new environment for assisting to solve the new optimization problem. Moreover, the environmental reaction scheme is also investigated in order to improve the ability of adapting to different kinds of dynamic environments. Experimental results on a series of DKPs with different randomly generated data sets indicate that the IRBPSO can faster track the changing environments and manifest superior statistical performance, when compared with peer optimization algorithms.

Plant defenses interact with insect enteric bacteria by initiating a leaky gut syndrome

Plants produce suites of defenses that can collectively deter and reduce herbivory. Many defenses target the insect digestive system, with some altering the protective peritrophic matrix (PM) and causing increased permeability. The PM is responsible for multiple digestive functions, including reducing infections from potential pathogenic microbes. In our study, we developed axenic and gnotobiotic methods for fall armyworm (Spodoptera frugiperda) and tested how particular members present in the gut community influence interactions with plant defenses that can alter PM permeability. We observed interactions between gut bacteria with plant resistance. Axenic insects grew more but displayed lower immune-based responses compared with those possessing Enterococcus, Klebsiella, and Enterobacter isolates from field-collected larvae. While gut bacteria reduced performance of larvae fed on plants, none of the isolates produced mortality when injected directly into the hemocoel. Our results strongly suggest that plant physical and chemical defenses not only act directly upon the insect, but also have some interplay with the herbivore's microbiome. Combined direct and indirect, microbe-mediated assaults by maize defenses on the fall armyworm on the insect digestive and immune system reduced growth and elevated mortality in these insects. These results imply that plant-insect interactions should be considered in the context of potential mediation by the insect gut microbiome.

To do or not to do: A concise update of current clinical controversies in immune checkpoint blockade.

Although programmed death-ligand 1 is currently the best available biomarker for first-line therapy with pembrolizumab for patients with non-small cell lung cancer and is a required companion test approved by the US Food and Drug Administration, programmed death-ligand 1 testing is an option (as a complementary test) for patients treated with nivolumab, atezolizumab, and durvalumab. Programmed death-ligand 1 expression is continuously variable and dynamic in the tumor microenvironment. Due to the complex molecular and cellular interactions involved in immune response, a single biomarker may not be sufficient to predict response to cancer immunotherapy. Integration of multiple tumor, immune response, and genomic parameters is likely to influence the future interpretation of biomarker-based treatment outcomes. This article, in a case-based format, concisely summarizes most up-to-date evidence in answering some commonly seen clinical controversies of cancer immunotherapy, in terms of (i) the predictive value of programmed death-ligand 1 as a biomarker; (ii) whether the use of steroids with checkpoint inhibitors will decrease efficacy of the latter; (iii) selection of patients for cancer immunotherapy based on immune-based response criteria, and (iv) whether the use of influenza vaccine with checkpoint inhibitors is considered safe. Until more robust, long-term prospective clinical data are available, these discussions may serve as a starting point for pharmacists to gain timely and effective management of these realistic issues.

Efficacy of mycobacterium phlei cell wall-nucleic acid complex (MCNA) in BCG-unresponsive patients.

342 Background: Previously, we reported the results of a single-armed, multi-institutional study on the efficacy of MCNA in patients who failed intravesical BCG treatment. Since that publication, a new standardized definition for BCG-unresponsiveness has been established. We re-analyzed the oncologic outcomes following intravesical MCNA in patients classified as BCG-unresponsive according to the new definition. Methods: Patients with recurring high grade NMIBC after intravesical BCG were enrolled. For this analysis, we focused on the patients satisfying the minimum criterion for adequate BCG treatment (5/6 induction and 2/3 maintenance). Treatment course included 6 weekly intravesical instillations of 8mg MCNA followed by 3 weekly instillations at months 3, 6, 12, 18, and 24. Followup assessments included cystoscopy, urine cytology and biopsy. Patients absent of high grade disease confirmed by central review of biopsy were deemed disease-free. Results: Of the 129 patients enrolled, 94 (68 CIS with/without papillary tumors, 26 papillary only tumors) fit the criteria for the new BCG-unresponsive definition. In the group with papillary tumors, DFS measured at months 6, 12, and 24 were 61.2%(38.2-77.8%), 61.2(38.2-77.8%), and 50.1%(27.5-69%). In the CIS-containing group, the corresponding DFS were 44.8%(32.3-56.4%), 26.5%(16.3-37.9%), and 16.6%(8.6-26.9%), respectively. Conclusions: Intravesical MCNA therapy has the potential to offer 26.5% of patients with CIS and 61.2% of patients with papillary tumors a chance to safely preserve their bladder for at least 1 year. The efficacy in BCG-unresponsive patients was higher than that reported with all-comers, suggesting that adequate priming with BCG might be required for further immune-based response.

Addressing issues of asthma in inner-city children

For children living in the inner city, asthma tends to be more frequent and severe. Although the causes for this heightened severity of asthma are not clearly established, environmental allergens likely play a major role. To characterize, understand, and treat children with asthma living in the inner city better, the National Institutes of Allergy and Infectious Diseases of the National Institutes of Health established an Inner City Asthma Program in 1991. Over the past 15 years, 3 separate inner-city asthma research networks have been formed and funded by this institute. The work from these programs has led to important observations including evidence that environmental allergens, particularly cockroach, are important for sensitization and severity of asthma of the affected children. Furthermore, reductions in the allergen load can lead to improved asthma control. The most recent program, the Inner City Asthma Consortium, was formed in 2002 with a goal to develop immune-based therapy for children with asthma in the inner city and to determine mechanisms of these therapies as well as immunopathogenesis of asthma in these high-risk children. This article reviews these programs and how they have begun the effort to understand and treat children with asthma who live in inner cities better and what their findings mean in relationship to unique features of asthma in inner city children.

RNAi is an antiviral immune response against a dsRNA virus in Drosophila melanogaster

Drosophila melanogaster has a robust and efficient innate immune system, which reacts to infections ranging from bacteria to fungi and, as discovered recently, viruses as well. The known Drosophila immune responses rely on humoral and cellular activities, similar to those found in the innate immune system of other animals. Recently, RNAi or 'RNA silencing' has arisen as a possible means by which Drosophila can react to a specific pathogens, transposons and retroviral elements, in a fashion similar to that of a traditional mammalian adaptive immune system instead of in a more generalized and genome encoded innate immune-based response. RNAi is a highly conserved regulation and defence mechanism, which suppresses gene expression via targeted RNA degradation directed by either exogenous dsRNA (cleaved into siRNAs) or endogenous miRNAs. In plants, RNAi has been found to act as an antiviral immune response system. Here we show that RNAi is an antiviral response used by Drosophila to combat infection by Drosophila X Virus, a birnavirus, as well. Additionally, we identify multiple core RNAi pathway genes, including piwi, vasa intronic gene (vig), aubergine (aub), armitage (armi), Rm62, r2d2 and Argonaute2 (AGO2) as having vital roles in this response in whole organisms. Our findings establish Drosophila as an ideal model for the study of antiviral RNAi responses in animals.

Biochemical and biological activities of 2,3-dihydro-6-[3-(2-hydroxymethyl)phenyl-2-propenyl]-5-benzofuranol (L-651,896), a novel topical anti-inflammatory agent

The biochemical and biological profile of a topical anti-inflammatory agent, 2,3-dihydro-6-[3-(2-hydroxymethyl)phenyl-2-propenyl]-5-benzofuranol (L-651,896), is described. L-651,896 inhibited the 5-lipoxygenase of rat basophilic leukemia cells with an ic 50 of 0.1 μM and leukotriene synthesis by human PMN and mouse macrophages with ic 50 values of 0.4 and 0.1 μM respectively. L-651,896 also inhibited prostaglandin E 2 synthesis by mouse peritoneal macrophages ( ic 50 = 1.1 μM). This compound inhibited ram seminal vesicle cyclooxygenase activity at considerably higher concentrations, and this effect was directly related to substrate concentration. When applied topically to the mouse ear, L-651,896 lowered elevated levels of leukotrienes associated with arachidonic acid-induced skin inflammation and delayed hypersensitivity induced by oxazolone. However, while L-651,896 inhibited the increased vascular permeability induced by arachidonic acid, it had no effect on the edema associated with the immune-based response to oxazolone in the same tissue. Thus, it is possible that leukotrienes may play a role in some but not all inflammatory responses.